Pharm Exam I Flashcards
aka Cranial-sacral
Parasympathetic
aka Thoraco-lumbar
Sympathetic
Effector and Function of alpha-1
smooth muscles and sphincters
contraction (constriction)
Effector and Function of alpha-2
Nerve endings
decrease transmitter release
Effector and Function of Beta-1
cardiac muscle and kidney
increase HR and contractility, increase renin
Effector and Function of Beta-2
smooth muscle (bronchi), liver, and skeletal muscle
relax smooth muscle, gluconeogenesis, increase K+
Effector and Function of Beta-3
Adipose
increase lipolysis
Effector and Function of DA-1
Smooth muscle (renal), mesenteric, and cardiac
relax renal SM
- higher doses activates B1 and A1 receptors
Pathway of catecholamine biosynthesis
Phenylalanine
Tyrosine
Dopa
Dopamine
Norepinephrine
Epinephrine
All catecholamines are rapidly inactivated by ___ and ___
MAO ro COMT
- Monoamine oxidase
- catechol-O-methyltransferase
What drugs should not be given with MAO inhibitors?
- antihistamines
- antihypertensives
- barbituates
- CNS depressants
- OTC cold meds
- tricyclic antidepressants
3 common MAO inhibitors
Nardil, Parnate, and Marplan
(3) naturally occuring catecholamines
Epinephrine, Norepinephrine, and Dopamine
(2) non-catecholamine sympathomimetics
Ephedrine and Phenylephrine
(2) Synthetic catecholamines
Isoproterenol and Dobutamine
(3) selective Beta-2 agonists
albuterol, metaproterenol, and terbutaline
(1) cardiac glycoside
digoxin
(2) phosphodiesterase inhibitor
Amrinone and Milrinone
Epinephrine doses for Cardiac arrest
0.1 ml/kg of 1:1000 ETT
or
0.1 ml/kg of 1:10,000 IV
Epinephrine dose for Status Asthmaticus
0.01 mg/kg of 1:1000 sq
Epinephrine storage and release
adrenal medulla
Administration of Epinephrine
oral administration is not effective
- Must use sub-q, IV, IM, IO, or via ETT
Why does Epi not affect the brain?
poorly lipid soluble
Cardiovascular effects of Epineprhine
increases HR by accelerating rate of phase 4 depolarization
- increase risk of dysrhythmias
- chronic Epi reduces plasma volume
Respiratory effects of Epinephrine
Bronchodilator
- unless patient is BB, then it causes bronchoconstriction from stimulating bronchial alpha receptors
Other effects of Epinephrine
- most significant effect on metabolism
- may activate Na+-K+ pump and transfer K+ into cells
- mydriasis
- accelerates coagulation
- increases total leukocytes
- increases factor V
Which catecholamines have no effect on Alpha?
Isoproterenol and Dobutamine
Which catecholamines have the greatest effect on Alpha?
Norepinephrine and Phenylephrine
Which catecholamine has no effect on Beta-1
Phenylephrine
Which catecholamines have the most effect on Beta-1
isoproterenol and dobutamine
Which catecholamine has the most effect on Beta-2
Isoproterenol
Which catecholamine is indirect and direct
Ephedrine
Which catecholamines have a negative impact on CO and HR?
Norepinephrine and Phenylephrine
Which catecholamine has a large negative effect on peripheral vascular resistance?
Isoproterenol
Which two catecholamines cause the greatest increase in peripheral vascular resistance and MAP?
Norepinephrine and Phenylephrine
Synthesis and storage of Norepinephrine
postganglionic sympathetic nerve endings
Norepinephrine in treatment of refractory hypotension
continuous infusion (2-16 ug/min) in severe sepsis
Side effects of Norepinephrine
- avoid in right ventricular failure
- increase venous return to heart and increases the pulmonary artery pressure
- may decrease CO and increase work of left ventricle
Low dose Dopamine
(0.5 - 3 mcg/kg/min)
- primarily stimulates D1 and D2
- increases splanchnic and renal flow
- diuresis
negative side effects of Dopamine
- tachycardia in high doses
- increased pulmonary vascular resistance
- not good for right heart failure
- does NOT provide renal protection
- may cause harm in patients with renal disease by redistributing blood flow in the kidney
Clinical use for Dopamine
increase cardiac output in patients with decreased contractility, low systemic blood pressure and low urine output
Cardiovascular effects of Dopamine
higher risk of developing sinus tachycardia and ventricular arrhythmias
Isoproterenol Overview
- most potent sympathomimetic
- no alpha effects
- rapidly metabolized by COMT
- neees a continuous infusion
Clinical uses of Isoproterenol
increases the HR in patients with heart block
- useful before insertion of pacemaker
- useful in pulmonary hypertension and right ventricular dysfunction
Adverse effects of Isoproterenol
vasodilation and decreased blood pressure
- can lead to myocardial ischemia
Dobutamine overview
Potent Beta-1, weak Beta-2 and increasing effect on Alpha at higher doses
- racemix mixture
- decreases pulmonary vascular resistance
- inhibits HPV
Clnical uses for Dobutamine
can improve cardiac output in patients with CHF and wean patients off cardiopulmonary bypass
- stress testing
- pulmonary hypertension
Ephedrine Overview
indirect alpha and beta agonist
- resistant to MAO in the GI tract
- drug can be absored after oral administration
- does not produce hyperglycemia
- CNS stimulation occurs
Clincial use for Ephedrine
increases systemic blood pressure
- tachyphylaxis occus
- no longer drug of choice for deliveries
Cardiovascular effects of Ephedrine
- less potent in raising BP and lasts approximately 10x longer than epinephrine
- increases systolic and diastolic BP, HR, and CO
Tachyphylaxis
second dose of a drug is less intense than the first
- occurs with many sympathomimetics
Phenylephrine Overview
synthetic noncatecholamine that mimics the effects of Norepineprhine, but is less potent and longer lasting
- increases venoconstriction
- must be double diluted
- increases coronary perfusion without chronotropic side effects
- good for CAD and aortic stenosis
Cardiovascular effects of Phenylephrine
peripheral vasoconstriction and increases systemic blood pressure, while decreasing CO
Phenylephrine Toxicity Treatment
- direct acting vasodilator (alpha antagonist)
- Ex: Phentolamine
- beta blockers are contraindicated
Digoxin Overview
Used for supraventricular tachydysrhythmias (paroxysmal atrial tachycardia, a-fib, and a-flutter)
- decrease conduction through the AV node
- 10-30min IV onset
Narrow Therapeutic range for Digoxin
- Causes
- renal dysfunction
- hypoxemia
- hypokalemia
- hypercalcemia
- hypermagnesemia
- Diagnosis
- plasma concentration
- anorexia, nausea, vomiting
- EKG
- atrial and ventricular arrhythmias
- long PR or heart block
Digoxin Toxicity Treatment
- correct causes
- hypokalemia
- hypoxemia
- Phenytoin, lidocaine, or atropine
- treat cardiac dysrhythmias
- temporary pacemaker
- if complete heart block
Contraindications for Digoxin
- Hypertrophic obstructive cardiomypathy (HOCM)
- IHSS
- ASH
- increased contractility may exacerbate outflow obstruction
- Wolff-Parkinson-White syndrome
IHSS
idiopathic hypertrophic subaortic stenosis
ASH
asymmetric septal hypertrophy
WPW EKG
short PR interval with delta wave

Selective Phosphodiesterase Inhibitors
- increase cAMP in myocardial and vascular
- increased inward Ca2+ current
- increases contractility
- vasodilation
- effective in BB patients
- enhance actions of catecholamines
Effects of Phosphodiesterase Inhibitors
- decrease SVR, PVR, and CVP
- increase contractility (inotropy)
Uses for Calcium
- after massive transfusion
- CP bypass
- following parathyroidectomy
How should calcium chloride be given?
through a central line
- always aspirate first
(2) Alpha Antagonists
Phentolamine and Phenoxybenzamine
(4) Alpha-1 antagonists
- Prazosin (minipress)
- Doxazosin (cardura)
- Terazosin (hytrin)
- Tamulosin (flomax)
(2) Alpha-2 Agonists
Clonidine and Dexmedotomidine
(2) Combinded Alpha and Beta Antagonists
Labetolol and Carvedilol
(6) Calcium Channel Blockers
- Amlodipine
- Diltiazem
- Nicardipine
- Nifedipine
- Nimodipine
- Verapamil
Primary mechanism of Norepinephrine termination
reuptake
preganglionic neurtransmitter of the parasympathetic system
acetylcholine
preganglionic neurotransmitter of the sympathetic system
acetylcholine
postganglionic neurotransmitter of the sympathetic system
Norepinephrine
Sensitivity for Alpha and Beta receptors
Alpha-1 NE > Epi
Alpha-2 NE > Epi
Beta-1 Epi >= NE
Beta-2 Epi > NE
locations of Alpha-1 receptors
- vascular smooth muscle
- heart
- GI smooth muscle
- liver
locations of Alpha-2 receptors
- CNS
- nerve endings
- vascular smooth muscle
- platelets
- pancreas
locations of Beta-1 receptors
heart and kidney
locations of Beta-2 receptors
smooth muscle and skeletal muscle
Alpha-1 agonism
smooth muscle contraction
Alpha-2 agonism
inhibition of NE release at the presynaptic terminal
Alpha blockers
prevent the effects of catecholamines and sympathomimetics on the heart and vasculature
- Side effects:
- orthostatic hypotension
- reflex tachycardia
- impotence
Phentoloamine
(regitine)
non-selective alpha antagonist
- used in hypertensive emergencies
- pheochromocytoma
- hyperreflexia
- Alpha 1 and 2
Phenoxybenzamine
(dibenzyline)
non-reversible and non-selective alpha antagonist
- administered orally
- give 10-14 days before pheochromocytoma removal
- may cause orthostatic hypotension
- may be useful in Raynaud’s disease
Symptoms of Pheochromocytoma
- sporadic elevations in blood pressure
- diaphoresis
- headaches
- palpitations
- anxiety/panic attacks
- malignant hypertension
Pre-op preparation for Pheochromocytoma removal
- Outpatient
- alpha blockade (phenoxybenzamine)
- titrate alpha blocker
- add CCB if needed
- add BB for tachycardia
- Inpatient
- fluid replacement
In a patient treated with propranolol and phenoxybenzamine prior to resection of a solitary pheochromocytoma, would you expect postoperative hypotension or hypertension?
Hypotension
- hypovolemia
- residual beta block
- adrenal insufficiency
- residual alpha block
Doxazosin
(Cardura)
used for hypertension and BPH
- relaxes prostatic and vascular smooth muscle
- Alpha-1
Prazosin
(minipress)
used for hypertension and CHF
- dilates arterioles and veins
- Alpha-1
Terazosin
(Hytrin)
treats BPH
- Alpha-1
Tamulosin
(Flomax)
treats BPH and may cause orthostatic hypotension
- Alpha-1A
Alpha-2 Receptor Agonists
- act like Alpha-1 antagonists
- mostly in CNS
- reduce norepinephrine release by a negative feedback system
Clonidine
- used to treat hypertension
- decrease HR and BP
- central sedative effect
- added to regional anesthetics
Dexmedetomidine
- sedative and analgesic
- metabolized in liver
- liver impairment dramatically impairs plasma level and duration
- withdrawal may occur
Response of Beta-1
increase heart rate and contractility
Response of Beta-2
bronchial and vascular SM relaxation
How much beta receptors in the heart are Beta-1?
75%
Treatment of Acute Coronary Syndrome
- treat with BB for acute MI
- unless severe bradycardia, unstable LV failure, or AV block
ST depression vs elevation
Depression signifies a reversible ischemic event that is happening currently
Elevation signifies damage has already been done
Perioperative BB
- used in high risk surgeries
- thoracic, intraperitoneal, vascular
- maintain 65-80 bpm
- Atenolol or Metoprolol
- POISE Study
- prevents nonfatal MI, but increases risk of stroke, death, hypotension, and bradycardia
Treatment drugs for Intraoperative MI
- Esmolol
- Metoprolol
- Atenolol
- Propanolol
Management of CHF
- improved survival with oral:
- Metoprolol
- Carvedilol
- Bisoprolol
Treatment for BB Toxicity
- Atropine
- Isoproterenol
- Dobutamine
- Glucagon
- Calcium Chloride
Also external or transvenous pacing and/or dialysis
Contraindication of nonselevtice B-blockers
bronchial asthma
Beta-1 Blockers and Diabetics
can impair recovery of hypoglycemia and mask symptoms of hyperglycemia
Which BB does not cross the placenta?
Esmolol
Contraindications to Beta Blockers
- Dysrhythmias
- first degree heart block
- second degree Type II
- third degree
- sinus arrest
- sick sinus syndrome
- hypovolemia with compensatory tachycardia
- COPD (relative)
- unopposed alpha stimulation
- cocaine abuse
- pheochromocytoma therapy
Propranolol
(Inderal, Ipran)
- Beta blocker
- pure antagonist
- lacks intrinsic sympathomimetic activity
- highly protein bound
- heparin will decrease bound drug
- increased local anesthetic toxicity
- especially Bupivicaine
*
- especially Bupivicaine
Esmolol
(Brevibloc)
- quick onset and offset
- selective B1-blocker
- caution in treatment of excess sypathetic outflow
- beta blockade results in unopposed alpha activity
Metoprolol
(lopressor)
- beta-1
- large doses become non-selective
- oral and IV
Timolol
Beta-1 and Beta-2 used for glaucoma
- systemic absorption can cause bradycardia and increased airway resistance
Labetalol
(Trandate)
Beta blocker and Alpha-1
- Uses
- hypertension and pregnancy induced
- intuabtion and emergence
- controlled hypotension
Carvedilol
(coreg)
beta and alpha-1 antagonist
- mild to moderate CHF
- hypertension
(2) CCB selective for AV node
benzothiazepines and Phenylalklamines
CCB selective for arteriolar beds
Dihydropyridines
Effects of CCB
- slow heart rate
- decrease speed of conduction through SA and AV node
- reduce cardiac contractility
- relax vascular smooth muscle
Uses for CCB
- Coronary artery spasm
- chronic and stable angina
- Supraventricular tachycardia (SVT)
Prinzmetals Angina
coronary artery spasms
Phenylalkylamine
(verapamil)
- Used in SVT, a-fib, and a-flutter
- slows conduction through AV node
- negative chronotropic effect on SA node
- negative inotrope
- vasodilates coronary and systemic arteries
May precipitate ventricular dysrhythmias in patients with WPW syndrome
(5) Dihydropyridines
- Nifedipine
- nicardipine
- Nimodipine
- Amlodipine
- Felodipine
Which CCBs increases or has no change to heart rate?
Nifedipine and Nicardipine
Which CCB has moderate SA depression?
Verapamil
Which CCBs have AV node conduction?
Verapamil > Diltizaem
Which CCB has the greatest coronary artery dilation?
Nicardipine
Cytoprotection
process by which chemical compounds provide protection to cells against harmful agents
Pacemaker Potential
Na influx, Ca influx, rapid Ca influx, K outflux
Phases of Cardiac Action Potential
- 0 - Na enters the cell (depolarizaton)
- 1 - close Na, open K
- 2 - Ca enters the cell (contraction)
- 3 - K exits the cell (repolarization)

Purkinje Fiber vs. SA node
- If is main source in Purkinje
- If and ICa in SA node
- Purkinje lower resting potential
- Purkinje steeper spontaneous depolarization slope
*
(2) basic mechanisms of arrhythmias
reentry and enchanced automaticity
Factors that facilitate arrhythmias
- hypoxemia
- electrolye imbalance
- myocardial ischemia
- atrial or ventricular enlargement
- alterted sympathetic nervous activity
- bradycardia
- certain drugs
Bradycardia predisposes what type of arrhythmias?
ventricular
If arrhythmias occur from volatile agents, they most likely arose from which mechanism?
re-entry
ECG and membrane potential of ventricular cell

Class IA antiarrhythmic
(example)
Procainamide
Class 1B antiarrhythmic
(example)
lidocaine
Class 1C antiarrhythmic
(2 examples)
flecainide and propafenone
Class II antiarrhythmic
(example)
esmolol
Class III antiarrhythmic
(2 examples)
amiodarone and sotalol
Class IV antiarrhythmic
(2 examples)
verapamil and diltiazem
Class 1 agents
inhibit fast sodium channels during depolarization
(phase 0)
- decreases in depolarization rate and conduction velocity
Class 1A effects
- Sodium channel blockade
- length action potential
- lengthen refractory period
- Potassium channel blockade
- prolonged repolarization
Side effects of Quinidine
- low therapeutic ratio
- allergic reaction
- accentuates effects of NMB
Procainamide
treats ventricular tachyarrhythmias
- class 1A
- drug of choice for stable V-tach
Class 1B antiarrhythmics
- less powerful than sodium blockers
- shorten the action potential duration and refractory period
- opposite of Class 1A
Side effects of phenytoin
- hypotension
- bone marrow suppression
- thrombocytopenia
Class 1C antiarrhythmics
- potent sodium blockers
- decrease rate of phase 0 depolarization
- decrease speed of conduction
- little effect on duration of AP and refractory period
- inhomogeneity
- proarrhythmic effect
- given if failed conversion from A-fib
- not the first choice
Class II antiarrhythmics
- Beta Antagonists
- decrease rate of spontaneous (phase 4) depolarization
- decrease ANS activity
- supression of ventricular activity during MI
- treats arrhythmias due to SNS activity
- a-fib and a-flutter
Effective beta blockade
55-60 bpm
side effects of beta blockers
- bradycardia
- hypotension
- myocardial depression
- bronchospasm
Class III antiarrhythmics
- blocks potassium channels
- prolongation of depolarization, action potential duration, and refractory period
Pulmonary toxicity of Amiodarone
- pneumonitis
- high FiO2 may accelerate reactions
- restrict inspired O2 to lowest necessary
- can be slow or acute
Amiodarone side effects
- inhibits p450 enzymes
- increases plasma concentrations of digoxin, procainamide, quinidine, and warfarin
- decreases digoxin
- increasesd effect of Warfarin because amiodarone depresses Vitamin K
- thyroid dysfunction
- has a high iodine content
- exhibits class I, class II, and class IV
Sotalol side effects
- tosade de pointes
- bradycardia
- not recommended in patients with asthma, ventricular dysfunction, and prolonged QTc intervals
Class IV antiarrhythmics
- inhibits inward slow Ca currents
- decreased rate of sponatenous phase 4 depolarization
- controls the ventricular rate in a-fib and a-flutter
Half life of Adenosine
10 seconds
Adenosine
- slows conduction through AV node
- temporarily stops heart
- used to treat SVT
Proarrhythmic effects of antiarrhythmics
- torsades de pointes
- ventricular tachycardia
- wide complex ventricular rhythm
Which antiarrhythmic is recommended prophylactically (oral)?
Amiodarone
Which class of antiarrhythmics experienced a higher incidence of sudden cardiac arrest?
Class IC
(flecainide and propafenone)
automatic implantable cardiac defibrilator (AICD)
placed if EF less than 30% or intractable arrhythmias

sustained V-tach
treat with amiodarone, lidocaine, or shock

Torsade’s de Pointes
treat with magnesium and shock
patients with unstable tachycardia should be treated immediately with _____
synchronized cardioversion
Amiodarone
- Beta Antagonist
- contains iodine
- dilates coronary arteries and increase coronary blood flow
Which Class of Antiarrhythmics decrease phase 0 (depolarization rate)?
1A and 1C
Which class of Antiarrhythmic drugs do not decrease the conduction velocity?
1B and IV
Which class of Antiarrhythmic drugs decrease the refarctory period?
1B and II
Which class of Antiarrhythmic drugs increase the QRS duration?
1A, 1C, and III
Which class of Antiarrhythmic drug has no effect on automaticity?
Class IV
Which class of Antiarrhythmic drugs inhibit slow calcium channels?
Class IV
Which class of Antiarrhythmic drugs inhibit potassium channels?
Class III
Which class of Antiarrhythmic drugs inhibit fast sodium channels?
Class I
Pacemaker Potential


Norepinephrine increases the slope of repolarization therefore increasing the heart rate